This study is designed to investigate a possible CNS GABA component in the pharmacotherapy and psychopathology of affective disorders. This hypothesis is based upon clinical data which suggests a possible decrease in GABA in the CSF of depressed patients. It is proposed that known anti-depressant drugs, from different pharmacological classes, will share certain pharmacological characteristics with GABAergic drugs in altering synaptic events mediated by GABA or norepinephrine. Specifically we will test the hypothesis that long-term (1-3 week) treatment with anti-depressants (imipramine, nomifensine, iprindole) or GABA agonists (progabide, THIP, baclofen) will reduce of number of beta-adrenergic binding sites (labelled by dihydroalprenolol) and GABA binding sites (labelled by GABA), in one or more region of the mouse brain as preliminary evidence suggests. These effects will be further characterized by examining potential changes in GABA receptor subtypes (A or B) after long-term drug treatment and by examining the effects of drugs with a predominant effect on one subtype. In addition, preliminary studies designed to provide the mechanistic basis for the expected receptor changes will be initiated (i.e., the relative contribution of pre- and post-synaptic events). These studies are expected to provide evidence in favor of a GABAergic mechanism in the action of anti-depressant drugs and to provide a rationale for the use of GABAergic drugs in affective disorders.